The analysis of liquid samples by sample analysis systems which utilize gas-phase or particle detectors, such as inductively coupled plasma (ICP) atomic emission spectrometers, is well known. Typically, such sample analysis systems require that a sample solution first be nebulized into sample solution droplets. The sample solution droplets are then typically desolvated to form nebulized sample particles which are then transported to, and injected into, a detector element of the sample analysis system, wherein the nebulized sample particles are analyzed. In ICP and other plasma sample analysis systems for example, the nebulized sample particles are injected into a high temperature plasma where they interact with energy present in the plasma to form fragments such as molecules, atoms and/or ions. Electrons in the molecules, atoms and/or ions are excited to higher energy state orbitals by said interaction. When the electrons relax back into their lower energy, more stable state, orbitals, electromagnetic radiation is emitted. The frequency of the emitted electromagnetic radiation is a "fingerprint" of the contents of the sample and the intensity of the emitted electromagnetic radiation is related to the concentration of the components in the sample.
There are numerous existing systems for producing nebulized sample solution droplets, (which are typically desolvated to form nebulized sample particles), for introduction into gas-phase or particle sample analysis systems. These include pneumatic spray nebulizers, thermospray nebulizers, high pressure jet-impact nebulizers, glass or metal frit nebulizers, total consumption nebulizers and ultrasonic nebulizers.
For decades pneumatic spray nebulizers were the most commonly used sample solution nebulizer systems for introduction of liquid samples in flame and plasma atomic spectrometry, (eg. atomic emission, atomic absorbtion and atomic fluorescence) as well as mass spectrometry. Pneumatic nebulizers operate by introducing a sample solution through a small orifice into a concentrically flowing gas stream. Interaction between the sample solution and the concentrically flowing gas stream causes production of nebulized sample solution droplets. Pneumatic spray nebulizers, however, produce a wide spectrum of sample solution droplets, as regards the diameter thereof, and limited aerosol sample solution droplet per volume density. This is because relatively large diameter sample solution droplets typically leave the pneumatic nebulizer system under the influence of gravity. Sample analysis systems generally, it will be appreciated, operate with greater sensitivity and provide results which are more reproducible when large numbers of nebulized sample solution droplets are presented for analysis therein, which nebulized sample solution droplets are of a relatively constant and small, (eg. 13 microns or less) diameter. This is because smaller droplets provide smaller desolvated sample particles which are more easily fragmented to produce molecules, atom and/or ions. It is noted that the diameters of sample solution droplets formed by a pneumatic nebulization process are dependent on the concentrically flowing gas flow rate and on the size of the small orifice.
A more recently developed approach to nebulizing sample solutions involves use of thermospray nebulizers. Thermospray nebulizers control the temperature of the tip of a capillary tube such that solvent in a sample solution presented thereto, through said capillary tube, is caused to vaporize. The result of said solvent vaporization is formation of nebulized sample solution droplets. Thermospray nebulizers are typically used with mass spectrometer analysis systems as they operate best in low pressures, such as those present at the inlet stages of mass spectrometers. U.S. Pat. Nos. 4,883,958 and 4,958,529 and 4,730,111 to Vestal describe such nebulizing systems. It is noted that the diameters of sample solution droplets formed by the thermospray process are dependent upon the temperature of the capillary tube. It is also noted that the use of elevated temperatures can degrade sample analytes.
A Patent to Willoughby, U.S. Pat. No. 4,968,885 teaches a nebulizing system which uses both thermospray and pneumatic means. Sample solution droplets produced by the process of this nebulizing system have diameters which depend on both temperature and a gas flow rate.
A jet-impact nebulizing system is described by Doherty et al. at (Appl. Spec. 38, 405-412, 1984). Said sample solution nebulizing system operates by forcing a sample solution through a nozzel which has an orifice therein on the order of twenty-five (25) to sixty (60) microns in diameter. The ejected sample solution impacts a wall and the interaction therewith causes formation of sample solution droplets. Again, sample solution droplet diameters depend on a flow rate as well as a driving pressure.
A glass frit nebulizer system is described by Layman et al. (Anal. Chem. 54, 638, 1982). A porous glass frit with numerous pores of a diameter from four (4) to eight (8) microns therethrough is positioned in the flow path of a sample solution. Sample solution which emerges therefrom is highly nebulized but the flow rate of the sample solution is typically low, (eg. five (5) to fifty (50) microliters/min). While providing well nebulized sample solution droplets, this nebulizer system is prone to inconsistent sample solution flow rates, and must be subjected to repeated wash cycles between applications. It is noted that sample solution droplet diameters are dependent on a driving sample solution pressure.
Total consumption nebulizing systems are taught in U.S. Pat. No. 4,575,609 to Fassel et al., and by Baldwin and McLafferty (Org. Mass Spect. 7, 1353, 1973). These nebulizing systems have the important advantage of being able to provide all of the analyte in a sample solution entered thereto, to the detector element in an analysis system. Sample carry-over from one analysis procedure to a subsequent analysis procedure is also minimized by the relatively very small internal volume thereof. Very low flow rate capacity, (eg. one (1) to one-hundred (100) microliters/min), however, limits the total amount of analyte in a sample solution entered thereto which can reach a detection element in an analysis system. As a result analysis system sensitivity is not greatly improved by their use. It is noted that sample solution droplet diameters depend on a pressure driven sample solution flow rate.
The above presentation shows that the nebulizing systems surveyed present with various operational limitations. For instance, sample solution droplets produced by pneumatic, jet-impact and thermospray nebulizer systems, or combinations of thereof, have diameters which are dependent on gas flow rates or potentially sample degrading high temperatures. In addition, the glass frit and total consumption sample solution nebulizers have inherent limitations as regards the amount of sample which they can nebulize and depend on a sample solution driving pressure to control sample solution droplet diameters. Said limited sample handling capability in these systems leads to a limit on the sensitivity of sample analysis systems which utilize them. An efficient sample solution nebulizer system which would produce droplets with diameters determined by some independent variables other than a potentially sample analyte degrading elevated temperature, and which allows high sample volume flow handling capabilities would therefore be of utility. The identified attributes are associated with ultrasonic nebulizer systems.
Briefly, ultrasonic nebulizer systems generally provide means to impinge a sample solution onto, or in close proximity to a vibrating piezoelectric crystal or equivalent which is a part of an oscillator circuit. Typically the oscillator circuit system is calibrated so that radio frequency vibrations are produced. Interaction between the vibrational energy produced by the vibrating piezoelectric crystal or equivalent and the impinging sample solution causes the later to become nebulized into sample solution droplets as a result of the instability of the liquid-gas interface when exposed to a perpendicular force.
It is important to understand that the sample solution droplets produced by ultrasonic nebulizers have diameters which depend on the frequency of vibration of the piezoelectric crystal or equivalent, and that when the frequency of vibration is set to a megahertz level, a theoretically large number (eg. seventy (70%) percent) of sample solution droplets can be formed with a relatively small uniform diameter of thirteen (13) microns or less. The important limitations of the sample solution nebulizer systems disclosed above are not present, (eg. sample solution droplet diameters are not dependent on potentially sample analyte degrading elevated temperatures or any flow rates or pressures). Ultrasonic sample solution nebulizing systems are also capable of handling relatively high sample flows, and the sample solution droplet diameters produced by ultrasonic nebulizer system also tend to be more consistent than the diameters of sample solution droplets produced by other nebulizing systems. In addition, the conversion rate of sample solution to nebulized sample solution droplets is theoretically relatively high, being higher than ten (10) to fifty (50%) percent as compared to approximately two (2%) percent when pneumatic nebulizer systems are used.
The presence of a far larger number and proportion of sample solution droplets with relatively small diameters means two things. First, less sample analyte is lost as a result of relatively large droplets falling away from entry to a detector element in a sample analysis system under the influence of gravity, hence, more sample analyte will be presented to said detector element; and second, the presence of smaller diameter sample solution droplets leads to production of smaller desolvated sample particles which are easier to fragment into molecules, atoms and/or ions for analysis. A larger amount of sample analyte is thus produced per fragmented sample particle. As a result, the sensitivity of a sample analysis system is improved when ultrasonic sample solution nebulizers are used, rather than other sample solution nebulizer systems.
A Patent to Olsen et al., U.S. Pat. No. 4,109,863 describes an ultrasonic nebulizer system in which a piezoelectric crystal or equivalent, (termed a transducer in Olsen et al.) is secured to the inner surface of a glass plate, which glass plate forms a leading portion of an enclosed hollow body, which hollow body is positioned in an aerosol chamber. The purpose of the glass plate is to provide the transducer protection against corrosion etc. which can result from contact with components in sample solutions. The glass plate thickness is typically one-half (0.5) wavelengths of the transducer vibrational wavelength utilized. This thickness optimizes effective transfer of vibrational energy therethrough. During use a sample solution is impinged upon the outer aspect of the glass plate, inside the aerosol chamber, rather than onto the transducer per se. The transducer is caused to vibrate and the interaction between the impinging sample solution and the vibrational energy produced causes production of nebulized sample solution droplets. In addition, a liquid coolant is circulated within the hollow body to maintain the transducer at a desired temperature. Problems which users of the Olsen et al. invention have experienced result from the use of a liquid to cool the transducer, and the use of a carrier gas injected from below the location of the transducer in the aerosol chamber. (It is noted that said carrier gas serves to sweep nebulized sample solution droplets toward a detector element in an analysis system). Even though the piezoelectric crystal is oriented vertically, bubbles tend to form on the back side of the transducer during use, resulting in uneven cooling of the transducer. This leads to reduced operational efficiency and lifetime of the transducer. In addition, the electrical leads to the transducer, from the other components of an oscillator circuit, pass through the cooling liquid, and they tend to become corroded during use. Continuing, injecting a carrier gas into the aerosol chamber from a position below the location of the piezoelectric crystal or equivalent, as is done in the Olsen et al. ultrasonic nebulizer system, leads to pulsations in the volume density of the aerosol sample solution droplets which ar produced over time which are available to sample analysis systems. In addition, the hollow body of the Olsen et al. invention is attached to the aerosol chamber thereof in a manner which creates "crevasses" therebetween. Sample from one analysis procedure can accumulate in the crevasses and by a "carry-over" capillary action or "wicking" effect be released and contaminate analysis results In subsequent analysis procedures. Continuing, the Olsen et al. invention directs nebulized sample solution droplet flow toward solvent vaporization, desolvation and sample analysis system detector elements by way of a relatively small diameter orifice. Turbulence results when the nebulized sample solution droplets pass through said relatively small diameter orifice and nebulized sample solution droplets are caused to reagglomerate, and are lost, as a result thereof. Finally, the hollow body construction of the Olsen et al. invention does not provide any vibrational energy focusing capability, since the vibrational energy produced by the transducer is emitted in all directions therefrom, without any means being present to redirect any of said vibrational energy.
A patent to Dorn et al. U.S. Pat. No. 4,980,057 describes a sample solution nebulizer system which uses both ultrasonic and pneumatic means to nebulize sample solutions. A one-sixteenth (1/16) inch stainless steel tube is placed in the center of an ultrasonic nebulizer probe and serves to concentrate the vibrational energy produced by an ultrasonic transducer present therearound. A fused silica capillary tube is placed inside the one-sixteenth (1/16) inch stainless steel tube to, during use, deliver a high velocity gas stream to the tip of the ultrasonic nebulizer probe. Also during use, the sample solution is introduced to the surface of the ultrasonic nebulizer probe. Interaction between the sample solution, vibrational energy and high velocity gas stream causes the sample solution to be nebulized into sample solution droplets. It is noted that this system probably can not utilize megahertz level frequencies as the ultrasonic nebulizer probe is not of a small enough dimension, (eg. on the order of half a wavelength of a megahertz vibrational frequency), to efficiently transmit megahertz wavelength vibrational energy waves to the location at which the sample solution is entered to the system. The Dorn et al. Patent teaches the use of one-hundred-and-twenty (120 KHZ) Kilohertz operational frequency. In addition, this system produces sample solution droplets, the diameters of which are affected by the flow rate of the sample solution nebulizing gas, as is the case with any pneumatic type sample solution nebulizing system.
A paper by Goulden et al. (Anal. Chem 56, 2327-2329, 1984) describes a modified ultrasonic nebulizer. The piezoelectric crystal or equivalent, termed a transducer in the Goulden paper, is oriented horizontally at the upper aspect of a glass container. A rubber stopper is placed below the transducer, inside the walls of the glass container. The rubber stopper has a vertically oriented centrally located hole therethrough such that a large amount of cooling water, (eg. one-half (0.5) l/min) can be caused to flow vertically upward through said vertically oriented centrally located hole in the rubber stopper, into the space between the lower surface of the transducer and the upper surface of the rubber stopper, and out thereof around the edges of the rubber stopper and inside the glass container. The purpose of the described arrangement is to prevent bubbles from accumulating under the transducer during use, and thereby avoid instabilities of operation and reduced transducer lifetime.
A paper by Karnicky et al. (Anal. Chem., 59, 327-333, 1987) describes another design for an ultrasonic nebulizer. An enclosed chamber has, at a distance above the inside surface of its lower extent, a piezoelectric crystal or equivalent, termed an ultrasonic transducer in the Karnicky paper, which ultrasonic transducer fits snugly within the inner side walls of the enclosed chamber. Air is present between the upper surface of the lower extent of the enclosed Chamber, and the lower surface of the ultrasonic transducer, but between the upper surface of the ultrasonic transducer and the lower surface of a glass diaphragm which is present at the upper aspect of the enclosed chamber, there exists a space through which cooling water is flowed during use. The ultrasonic transducer is shaped concave upward so that vibrational energy produced thereby during use is directed to and focused upon the glass diaphragm through the cooling water. An enclosed sample solution entry and carrier gas entry assembly mounts to the enclosed chamber above the location of the glass diaphram. During use the enclosed chamber with ultrasonic transducer therein, and with the enclosed sample solution and carrier gas entry assembly mounted thereto is oriented with its longitudinal axis at an approximate forty-five degree angle to an underlying horizontal surface. A sample solution is entered so that it impinges on the outer surface of the glass diaphragm at an approximate forty-five degree angle thereto. Interaction between vibrational energy produced by the ultrasonic transducer and the impinging sample solution produces nebulized sample solution droplets which are then transported to desolvation and solvent removal systems under the influence of a pressure gradient created by the entering of a carrier gas flow to the enclosed sample solution and carrier gas entry assembly. It is also noted that the Karnicky system provides a wick which contacts the outer surface of the glass diaphragm to drain away sample solution which is not nebulized during use.
Another paper, by Mermet et al. (Dev. Atomic plasma Spec. Anal. proc. Winter Conference, 245-250, 1980), describes yet another design for an ultrasonic nebulizer system. A piezoelectric crystal or equivalent, termed a transducer in the Mermet paper, is present within a waveguide structure which decreases in inner diameter along its upwardly projecting longitudinal axis, near the lower extent thereof. The internal waveguide structure is thus, conical in shape, and during use is filled with a vibrational energy transmitting bath. Said waveguide structure shape plays the role of an impedance transformer and use of low electrical power levels, (eg. five (5) to seven (7) watts) to effect sample solution nebulization is made possibly, thereby reducing transducer cooling requirements. At the upper extent of said waveguide structure is present a nebulization cell, the lower extent of which is made from a thin membrane of ethylene polyterephtalate (Mylar, Terphane) which is transparent to ultrasonic energy vibrational energy. During use a sample solution is entered to the nebulization cell and vibrational energy produced by the transducer is directed by the waveguide structure through the vibrational energy transmitting bath into the nebulization cell where it interacts with the entered sample solution to form sample solution droplets. Said nebulized sample solution droplets are then transported to additional sample preparation stages under the influence of a pressure gradient created by entering a carrier gas flow to the nebulization chamber.
The above summary of relevant references shows that while ultrasonic nebulizer systems provide benefits as compared to other nebulization systems, problems still exist. Problems with operational stability and piezoelectric crystal or equivalent lifetime develop as a result of uneven cooling thereof during use, when bubbles form in a cooling liquid where it meets the piezoelectric crystal or equivalent. In addition, ultrasonic energy produced by a vibrating piezoelectric crystal or equivalent in most ultrasonic nebulizer systems is not well directed for use in nebulizing a sample solution, to a point at which a sample solution is present. Other problems result from injecting a carrier gas meant to carry nebulized sample solution droplets toward a detector in a sample analysis system, at nonoptimum locations and in nonoptimum directions. This leads to formation of turbulence in nebulized sample solution droplet flows and accompanying reagglomeration of nebulized sample solution droplets This effect is worsened by the presence of relatively small orifices in the flow paths of nebulized sample solution droplets present in the aerosol chambers of some inventions. Also, the presence of crevasses in the aerosol chamber of some inventions leads to sample carry-over from one analysis procedure to a subsequent analysis procedure. Additional complications result, in some inventions, from the use of pneumatic nebulization means in addition to ultrasonic means, and from the use of system geometry which limits the ultrasonic nebulizer operational frequency to less than megahertz levels.
Continuing, as mentioned at the outset, sample preparation for introduction to a detector element in a sample analysis system typically involves not only a sample solution nebulization step, but also sample desolvation and solvent removal steps. Nebulized sample solution droplets are typically desolvated prior to being entered, for instance, to an ICP. If this is not done, plasma instability and spectra emission interference can occur in plasma based analysis systems, and solvent outgassing in MS systems can cause pressures therein to rise to unacceptable levels.
Desolvation of sample solution droplets involves two processes. First, sample solution droplets are heated to vaporize solvent present and provide a mixture of solvent vapor and nebulized sample particles; and second, the solvent vapor is removed. The most common approach to removing solvent is by use of low temperature condenser systems. Briefly, in said low temperature condenser systems the nebulized sample solution droplets are heated to vaporize the solvent present, and then the resulting mixture of solvent vapor and nebulized sample particles is passed through a low temperature solvent removal system condenser. When the solvent present is water very high desolvation efficiency, (eg. ninty-nine (99%) percent), is typically achieved, when the solvent condensing temperature is set to zero (0) to minus-five (-5) degrees centigrade. However, when organic solvents are present the desolvation efficiency at the indicated temperatures is typically reduced to less than fifty (50%) percent. Use of lower temperatures, (eg. minus-seventy (-70) degrees centigrade), can improve the solvent removal efficiency, but will also cause greater loss of nebulized sample particles as an undesirable accompanying effect. In addition, low temperature desolvation systems typically comprise a relatively large volume condenser. This leads to sample "carry-over" problems from one analysis procedure to a subsequent analysis procedure as it is difficult to fully flush out the relatively large volume between analysis procedures.
A Patent to D'Silva, U.S. Pat. No. 5,033,541 describes a high efficiency double pass tandem cooling aerosol condenser desolvation system which has been successfully used to desolvate ultrasonically nebulized sample droplets. This invention presents a relatively small internal condenser volume, hence minimizes sample carry-over problems, however, while the invention operates at high desolvation efficiencies when water is the solvent involved, it still operates at lower desolvation efficiencies when organic solvents are used. The invention also requires sample passing therethrough to undergo turbulance creating direction reversals, and the use of relatively expensive refrigeration equipments. Turbulance in a nebulized sample flow path can cause reagglomeration of nebulized sample solution droplets and, especially when very low temperatures are present, recapture of nebulized desolvated sample particles present.
A Patent to Skarstrom et al., U.S. Pat. No. 3,735,558 describes a counter-flow hollow tube(s) enclosed filter, mixed fluids key component removal system. Briefly, the invention operates to cause separation of key components from mixed fluids, such as water vapor from air, by entering the mixed fluid at one end of a single, or a series of, hollow tube(s), the walls of which are selectively permeable to the key components of the mixed fluid which are to be removed. A gas is entered to the system at the opposite end of the hollow tube(s), which gas is caused to flow over the outside of the hollow tube(s) in a direction counter to that of the mixed fluids, to provide an external purge of the key components of the mixed fluid which diffuse across the hollow tube(s). Diffusion of key components is driven by pressure and concentration gradients across the hollow tube(s . This approach to removal of diffusing components does not require the presence of low temperature producing refrigeration equipments, and presents a relatively small internal volume.
Two Patents to Vestal, U.S. Pat. Nos. 4,958,529 and 4,883,958 also describe systems which utilize counter-flow enclosed filters systems, with the application being to remove solvent vapor from nebulized samples produced by a spraying technique. The Vestal Patents state that the properties of the filter material used are not critical to the operation of the invention, but suggest the use of filter material available under the tradename of ZITEX. Said filter material provides a pore size of from two (2) to five (5) microns with a corresponding porosity of up to sixty (60%) percent. ZITEX is typically available in sheet form and enclosed filters made therefrom are typically constructed from a multiplicity of spacers and two sheets thereof. To provide an enclosed filter which is sufficiently long to provide reliable solvent vapor removal, in a reasonable space, it is typically necessary to arrange the spacers in a pattern which requires many severe sample flow path direction changes. A flow of solvent vapor and nebulized sample particles passing through such a tortuous pathway experiences turbulance. Turbulance causes sample to adhere and accumulate inside the enclosed filter thereby causing sample carry-over problems. The Vestal Patents also describe the heating of the enclosed filter to further assure continuous vaporization of solvent vapor present therein, and the flow of a gas outside the enclosed filter to remove solvent which diffuses through the enclosed filter.
The above presentation shows that the preparation of liquid samples for analysis in gas phase or particle analysis systems typically involves:
1. Nebulizing a sample solution to form sample solution droplets.
2. Desolvating the resulting nebulized sample solution droplets and removal of the solvent.
3. Transporting the sample through the nebulizing system, desolvation and solvent removal systems into a detector of an analysis system.
4. Doing the above with varying degrees of success as regards use with either water or organic solvents, minimizing sample carry-over from one analysis procedure to a subsequent analysis procedure and achieving long term stability of operation.
In view of the above it can be concluded that a sample introduction system which at once: provides high sample solution nebulization efficiency and aerosol conversion rate; produces sample solution droplets with diameters which are determined by an easily controlled independent parameter other than a potentially sample analyte degrading high temperature; allows entry of relatively high sample solution flow; provides more efficient, (more than ninty-nine and nine-tenths (99.9%) percent), desolvation of the produced nebulized sample solution droplets in a manner which is equally successful whether water or organic solvents are present; minimizes sample carry-over by increasing sample transport efficiency therethrough and which optimizes system long term operational stability, would be of great utility. Such a sample introduction system is taught by the present invention.